Biological Therapy in Primary Sjögren's Syndrome: Effect on Salivary Gland Function and Inflammation.

Michele Bombardieri,Anwar Tappuni,Farzana Chowdhury

doi:10.3389/fmed.2021.707104

Michele Bombardieri, Anwar Tappuni + Show 1 more

Open Access

https://doi.org/10.3389/fmed.2021.707104

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Abstract

Primary Sjögren's syndrome (pSS) is a chronic, systemic autoimmune disease. It is the second most common rheumatic autoimmune disorder, affecting 0.7% of European Americans and up to 1% of people globally. pSS is characterized by the impaired secretory function of exocrine glands, including salivary and lachrymal glands. A lymphocytic infiltration of these organs leads to the common and debilitating symptoms of oral and ocular dryness, majorly affecting the quality of life of these patients. Currently, no disease-modifying drug has been approved for the treatment of pSS, with therapies largely aimed at relieving symptoms of dry mouth and dry eyes. In particular, management of oral dryness still represents a major unmet clinical need in pSS and a significant burden for patients with this condition. Recently, several randomized clinical trials in pSS with biological therapies targeting specific mechanistic pathways implicated in the disease pathogenesis, including B-cell hyperactivity, T-cell co-stimulation and the aberrant role of cytokines, have been completed with mixed results. In this review, we summarize evidence from recent clinical trials investigating biological therapy in pSS, specifically highlighting efficacy, or lack thereof, in modulating local inflammation and improving salivary gland function.

Highlights

Primary Sjögren’s syndrome is described as a systemic autoimmune disease targeting the exocrine glands, mainly the salivary and lachrymal glands
The first positive randomized controlled trials (RCTs) was reported by Meijer et al, where 30 Primary Sjögren’s syndrome (pSS) patients with recent and active disease were tested with RTX, meeting its primary outcome measure: a significant improvement in salivary glandular function, as measured by the stimulated whole salivary flow (SWSF) rate
Based on our understanding of pSS pathogenesis and the mechanisms involving B-cells, T-cell co-stimulation and the complex network of cytokines, biologics have increased the armamentarium used for the potential treatment of this disease

Summary

INTRODUCTION

Primary Sjögren’s syndrome (pSS) is described as a systemic autoimmune disease targeting the exocrine glands, mainly the salivary and lachrymal glands. The first positive RCT was reported by Meijer et al, where 30 pSS patients with recent and active disease were tested with RTX, meeting its primary outcome measure: a significant improvement in salivary glandular function, as measured by the SWSF rate. This was reflected in subjective PROs of sicca symptoms, highlighting clinically meaningful improvements [15]. TRACTISS did not achieve its primary outcome of improvements based on patient-reported VASs (30% reduction in fatigue or oral dryness) [43], a significant difference was observed between the placebo and treatment arms when assessing glandular function [22].

B: T cell ratio

Findings

CONCLUSION